At a median follow-up of 14.2 months (range, 0.3-24.9), the overall response rate (ORR) among patients treated in part 2 of the study at the recommended phase 2 dose (RP2D) of 320 mg once daily (n = 103) was 52.4% (95% CI, 42.4%-62.4%; 1-sided P < .0001) per independent review committee (IRC) assessment. The IRC-assessed complete response (CR) rate was 15.5% (95% CI, 9.1%-24.0%) and the median time to response (TTR) was 1.9 months (range, 1.6-6.2) per IRC assessment.
“These results support sonrotoclax as a promising treatment option for patients with relapsed/refractory MCL,” Michael Wang, MD, lead study author and professor in the Department of Lymphoma/Myeloma and the Department of Stem Cell Transplantation in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, stated during a presentation of the data. “A phase 3 randomized clinical trial [CELESTIAL-RRMCL; NCT06742996] is ongoing to evaluate MCL response and duration of response [DOR] of sonrotoclax plus zanubrutinib [Brukinsa] vs a placebo group.”
In November 2025, the FDA granted priority review to a new drug application (NDA) seeking the approval of sonrotoclax for the treatment of adult patients with relapsed/refractory MCL who received a prior BTK inhibitor.2 The NDA was supported by data from BGB-11417-201.
How was the BGB-11417-201 study designed?
BGB-11417-201 enrolled adult patients with histologically confirmed MCL per World Health Organization 2016 classificiation.1 Patients also needed to have received at least 1 line of anti–CD20-based therapy and at least 1 prior BTK inhibitor, have an ECOG performance status of 0 to 2, and have no history of BCL2 inhibitor treatment.
During the dose escalation and safety expansion portions (parts 1A and 1B), patients received sonrotoclax at 160 mg once daily (target dose 1; n = 10) or at 320 mg once daily (target dose 2; n = 12). The safety expansion portion included up to 2 patient cohorts at select target dose levels of up to 12 patients per cohort. In the efficacy expansion portion (part 2), patients received the agent at the RP2D until disease progression.
The primary end points in parts 1A and 1B were the incidence of dose-limiting toxicities (DLTs), treatment-emergent adverse effects (TEAEs), serious adverse effects (AEs), AEs leading to treatment discontinuation, and tumor lysis syndrome (TLS) events. Preliminary antitumor activity was evaluated as a secondary end point. In part 2, the primary end point was ORR per IRC assessment. Secondary end points included investigator-assessed ORR, duration of response (DOR) by IRC and investigator assessment, progression-free survival (PFS) by IRC and investigator assessment, TTR by IRC and investigator assessment, health-related quality of life, overall survival (OS), and safety.
At baseline, the median age among patients who received sonrotoclax at the RP2D (n = 115) was 68 years (range, 39-85). Most patients were at least 65 years old (64.3%), male (75.7%), White (53.0%), not Hispanic or Latino (75.7%), had an ECOG performance status of 1 (64.3%), had stage IV disease at study entry (78.3%), and were refractory to their last line of treatment (87.0%).
The median number of prior lines of therapy was 3 (range, 1-8). All patients received a prior BTK inhibitor and 19.1% received 2 or more prior BTK inhibitors. Most patients received at least 3 prior lines of therapy (59.1%); prior therapy included CAR T-cell therapy (2.6%) and autologous stem cell transplant (14.8%). Reasons for stopping the last line of anticancer therapy consisted of progressive disease (68.7%), completion of treatment (14.8%), toxicity (10.4%), and other (6.1%).
What were the additional efficacy and safety data?
Additional findings from BGB-11417-201 showed that patients treated at the RP2D in part 2 achieved a median DOR of 15.8 months (95% CI, 7.4-not evaluable [NE]) by IRC; 63% of patients who achieved a response remained in remission after 9 months. The IRC-assessed median PFS and OS were 6.5 months (95% CI, 4.0-10.4) and not reached (NR; 95% CI, 14.8 months to NE), respectively.
The investigator-assessed ORR was 47.6% (95% CI, 37.6%-57.6%), including a CR rate of 22.3% (95% CI, 14.7%-31.6%). The investigator-assessed median TTR was 1.9 months (range, 1.6-4.0). The IRC-assessed ORR among patients who received less than 3 prior lines of therapy was 61.0% (95% CI, 44.5%-75.8%).
Findings from a subgroup analysis showed that subgroups with at least 5 patients that were evaluated in part 2 showed a consistently superior ORR benefit vs the historical control of 30%. The IRC-assessed ORR among patients with disease harboring a TP53 mutation (n = 22) was 59.1% (95% CI, 36.4%-79.3%).
In terms of safety, no DLTs were reported in part 1 of the trial and the maximum tolerated dose was NR. In the safety population (n = 115), any-grade TEAEs were reported in 96.5% of patients; 80.0% of these were deemed to be related to treatment. Grade 3 or higher TEAEs were reported in 52.2% of patients and 36.5% of events were treatment related. Serious TEAEs (37.4%), TEAEs leading to death (13.0%), TEAEs leading to treatment discontinuation (13.9%), and TEAEs leading to treatment modification (27.0%) were all reported.
The most common any-grade TEAEs included neutropenia (35.7%), thrombocytopenia (24.3%), and anemia (24.3%). Any-grade infections (39.1%), febrile neutropenia (1.7%), and TLS (7.0%) were reported. Among the patients who experienced TLS, 2 had clinical TLS and 6 had laboratory TLS. All TLS events were resolved without sequelae, and none resulted in death or the discontinuation of therapy.
“Treatment with sonrotoclax monotherapy was well tolerated and no new safety signals were identified,” Wang said. “The most common grade 3 or higher TEAEs were hematologic events and infections that were manageable and reversible.”
Disclosures: Wang received honoraria, research funding, or consultancy fees from Bioinvent, Juno, AstraZeneca, Dava Oncology, Oncternal, Nurix Therapeutics, Molecular Templates, South African Clinical Hematology Society, TG Therapeutics, Amphista Therapeutics, Catamount Medical Education, Miltenyi Biotech, Editorial Medica AWWE SA, Pharmacyclics, Roche, Acerta Pharma, Studio ER Congressi, Instituto Scientifico Romagnolo, Vincerx , BeOne, ADC Therapeutics, Juno Therapeutics, Bantam Pharma, Pepromene Bio, Beigene, Physicians Education Resources (PER), Genentech, Boxer Capital, NIH, Binaytara Foundation, PromCon S.R.E, Scripps, Plexus Communications, Celgene, Loxo, AbbVie, Gilead, MJH Life Sciences, Mayo Clinic, Deciphera, Janssen, VJHemOnc, Kite Pharma, CAHON, Galapagos NV, Bristol Myers Squibb, MSC National Research Institute of Oncology, Genmab, Research to Practice, Medscape/WebMD, Merck, and Lilly.
References
- Wang M, Song Y, Hermine O, et al. Sonrotoclax (BGB-11417) monotherapy in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) previously treated with a bruton tyrosine kinase (BTK) inhibitor: early results from a phase 1/2 study. Blood. 2025;146(suppl 1):663. doi:10.1182/blood-2025-663
- U.S. FDA grants priority review to sonrotoclax for the treatment of relapsed or refractory mantle cell lymphoma. News release. BeOne Medicines Ltd. November 26, 2025. Accessed December 8, 2025. https://ir.beonemedicines.com/news/us-fda-grants-priority-review-to-sonrotoclax-for-the-treatment-of-relapsed-or-refractory-mantle/786f1dad-0c9f-492e-9fce-f9ceadd24989
